Term
| How is a homestatic plug formed? |
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Definition
There has to be primary hemostatsis where the platelets aggregate, and then the secondary hemostatsis where the coagulation cascade has to take place.
NB that the common final pathway to the coagulation cascade is to form fibrin (NB that thrombin stimulates the formation of fibrin) |
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Term
| What are the 2 ways to regulate coagulation? |
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Definition
| Fibrin inhibition (protease inhibitors in plasma itself) or fibrinolysis (via activation of plasminogen to plasmin which degrades both fibrinogen and fibrin) |
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Term
| A summary of the Rxs used in disorders of coagulation are: |
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Definition
A) Rxs used to reduce clotting (Platelet aggregation inhibitors, anticoagulants, thrombolytics)
B) Rxs used in bleeding disorders (plasminogen activation inhibitors, protamine sulfate, vit. K, plasma fractions) |
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Term
| What are some of the platelet aggregation inhibitors? |
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Definition
Cyclooxygenase inhibitors (Aspirin)
ADP receptor blockers
Phosphodiesterase inhibitors
Blockers of platelet GP IIb/IIIA receptors (newest) |
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Term
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Definition
| Thromboxane A2 causes platelets to degranulate and aggregate, aspirin thus antagonises TXA2 synthesis via irreversible acetlating the enzyme COX (NB that new platelets come out every 10 days) |
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Term
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Definition
| Its coupled to Gq which activate PLC which gives u DAG and IP3, DAG goes and activates PKC and IP3 releases Ca2+ from stores. Both Ca2+ and PKC go and activate PLA2 which can make the low affinity GP IIb/IIIa receptor to fibrinogen to a high affinity one. Think of fibrinogen as a linker of two GP IIb/IIIa receptors on two platelets |
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Term
| What are the 3 uses of aspirin? |
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Definition
| Prophylactic Tx of transient cerebral ischemia and also to reduce the incidence of recurrent MI and to also reduce the mortality in post MI pts |
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Term
| What are ADP R blockers targeting? |
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Definition
| P2Y12 is irreveribly inhibited, its one of the two subtypes of ADP Rs on platelet surface. Clopidogrel is preferred over Ticlopidine cause it has fewer A/Es |
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Term
| How do phosphodiesterase inhibitors work? |
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Definition
| They inhibit cyclic nucleotide phosphodiesterases thus preventing the break down of second messengers like cAMP in this case. Weird enough it can also prevent the uptake of adenosine, which acts at A2 Rs to activate platelet Adenylyl cyclase |
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Term
| Whats the only phosphodiesterase inhibitor Rx? |
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Definition
| Dipyridamole, which by itself has little effect but when used with warfarin -> prophylaxis for thromboemboli in pts w/ prothetic heart valves; when combined w/ aspirin and an extended release form of dipyridamole -> secondary prophylaxis of CVS Dz (Tx angina via conronary vasodilation) |
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Term
| What are the most direct platelet aggregation inhibitors? |
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Definition
| Blockers of platelet GP IIb/IIIa Rs, New and used for acute coronary syndrome. NB that the R is for fibrinogen, vitronectin, fibronectin & vWF |
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Term
| What are the 3 Rxs that act on platelet IIb/IIIa Rs? |
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Definition
ABCIXIMAB - Abs
Eptifibatide - cyclic peptides, reversible
Tirofiban - nonpeptide, reversible |
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Term
| What are the 5 anticoagulants? |
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Definition
| UFH, LMWH, selective factor Xa inhibitor, Direct thrombin inhibitors (DTIs), Coumarins (oral warfarin) |
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Term
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Definition
| Injectable, rapid acting, is an anionic glycosaminoglycan, MW 15000 |
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Term
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Definition
| Antithrombin III is an alpha-globulin the inhibits serine proteases, including several clotting factors, eg. thrombin. With out heparin, antithrombin interacts w/ thrombin slowly, but upon binding to heparin rapid inhibition occurs, except to that already bound to fibrin. So basically a physiological process is sped up |
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Term
| How do u get LMWH from UFH? |
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Definition
| U use chemical or enzymatic depolymerization to cut off the part that forms the tertiary complex. NB that the tertiary complex is needed for accelerating the inactivation of IIa but not needed for factor Xa inactivation |
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Term
| What lab value is used to monitor heparin levels? |
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Definition
| aPTT (activated partial thromboplastin time) as it tests the intrinsic and common pathway coagulation. LMWH has a higher therapeutic index and thus does not need to be monitored. |
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Term
| What are some of the A/Es of heparin use? |
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Definition
| Heparin-induced Thrombocytopenia (HIT), bleeding and hypersensitivity |
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Term
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Definition
| Abs recoginise Heparin complexed to a platelet protein (Platelet factor 4), the FC portion of the Ab bindes to a R on the platelet to cause further degranulation and aggregation |
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Term
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Definition
| Discontinue heparin and give DTI (direct thrombin inhibitor) or fondaparinux (antidote?) |
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Term
| What is the antidote for heparin toxicity? |
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Definition
| Protamine sulfate as its cationic |
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Term
| What is the only selective factor Xa inhibitor Rx? |
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Definition
| Fondaparinux, its a synthetic pentasaccharide that binds to antithrombin III to cause a conformational change so it'd bind to factor Xa. Used to prevent or treat DVT, once a day SC injection |
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Term
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Definition
Lepirudin (synthetic derivative of hirudin)
Bivalirudin (synthetic derivative of hirudin)
Argatroban (small molecule thrombin inhibitor) |
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Term
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Definition
| Its a synthetic peptide derivative of hirudin (a powerful and specific thrombin inhibitor from a leech). NB that since it is independent of antithrombin III it can target fibrin-bound thrombin. Given parentally and monitored with aPTT (same as heparin) and no antidote exists |
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Term
| What are the 2 coumarins? |
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Definition
| Warfarin and Dicumarol (not really talked abt) |
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Term
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Definition
| It inhibits Vit. K Epoxide Reductase, which uses NADH to reduce the oxidised/ epoxide vit. K. NB that the Reduced Vit. K (active form) only gets to the Vit. K Epoxide (inactive) via being a cofactor for gamma-Glutamyl Carboxylase (which froms gamma-carboxy Glutamate residue from glutamate residues so that they have 2 carboxyl grps) |
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Term
| How do u reverse warfarin activity? |
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Definition
| It takes 12 hrs to take effect but w/ Vit. K their anticoagulant properties is reversed by 24 hrs |
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Term
| What lab value is used to monitor warfarin? |
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Definition
| Since it has a narrow TI and participates in many Rx-Rx interactions, one must check the levels of PT (prothrombin time) every 2-4 wks. It tests the extrinsic and common pathway of coagulation. NB that warfarin prolongs PT mainly by decreasing amount of functional factor VII |
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Term
| What are the A/Es of warfarin? |
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Definition
| Hemorrhage; cutaneous necrosis from reduced activity of protein C (which prevents bleeding???) during the 1st wk of Tx; crosses placenta -> hemorrhage and serious birth defects |
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Term
| What are the important Rx-Rx interactions of warfarin? |
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Definition
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Term
| What are the 4 fibrinolytics (thrombolytics)? |
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Definition
Streptokinase
Urokinase
Alteplase, Reteplase & Tenecteplase
Anistreplase
These all stimulate plasminogen to convert to plasmin |
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Term
| Plasminogen activation inhibitors are? |
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Definition
| Are the exact opposite of fibrinolytics as in they inhibit plasminogen activation. Ex. Aminocaproic acid |
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Term
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Definition
| Chemical antidote of heparin (cause its cationic due to its high arginine conc.) |
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Term
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Definition
| Warfarin antedote but needs 24 hrs thus for acute Tx use fresh-frozen plasma and infuse it |
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Term
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Definition
| When ur missing 90% of a factor u can have spontaneous bleeding. NB that Factor VII def (classic hemophilia or hemophilia A) and Factor IX def (Christmas Dz or hemophilia B) account for most of the heritable coagulation defects |
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